Click here to close now.




















Welcome!

News Feed Item

Study Identifies Targeted Molecular Therapy for Untreatable NF1 Tumors

CINCINNATI, Dec. 10, 2012 /PRNewswire-USNewswire/ -- Researchers conducting a preclinical study in mice successfully used targeted molecular therapy to block mostly untreatable nerve tumors that develop in people with the genetic disorder Neurofibromatosis 1 (NF1).

(Logo: http://photos.prnewswire.com/prnh/20110406/MM79025LOGO)

Scientists from Cincinnati Children's Hospital Medical Center report their findings online Dec. 10 in the Journal of Clinical Investigation.

"We can for the first time shrink the large majority of neurofibromas, at least in mice, by using a molecularly targeted treatment," said Nancy Ratner, PhD, principal investigator and program leader for the Cancer Biology and Neural Tumors Program in the Cancer and Blood Disorders Institute at Cincinnati Children's. "At present there is no treatment for these tumors and our data provide strong rationale for testing this therapy in clinical trials for NF1."

Neurofibromas are benign tumors that grow along peripheral nerves in the body. They affect up to half of the people who have NF1. In the United States alone there are 10,000 people with NF1. Fueled initially by mutation of the tumor-suppressing gene NF1, the tumors can grow to become quite large and compress vital organs. They can also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs), the leading cause of death in people with NF1.

The researchers tested an existing experimental drug from Pfizer called PD0325901, which in the current study shrank NF1 tumors in over 80 percent of the mice treated. Study authors report it was "the most dramatic result described to date for neurofibroma bearing mice."

The drug inhibits a protein called MEK, part of a molecular signaling chain that relays genetic instructions to the cell nucleus to promote cell growth. Researchers decided to test the drug after conducting a cross-species bioinformatics computer analysis of mouse and human NF1 tumors. The analysis identified genes and molecules that regulate cell signals driving the growth of neurofibromas and MPNSTs in both species.

The drug is currently being tested in human clinical trials for cancers that involve molecular components similar to those in NF1, in particular the MEK protein.

MEK is a downstream molecular target for a group of cell signaling proteins called Ras-GTPase. The proteins work together in a molecular relay to activate normal cell growth. In the instance of genetic mutation, Ras-GTPase can get stuck in the "on" position and promote hyperactive cell growth, tumor formation or cancer. Overactive Ras-GTPase signaling has been linked to a number of cancers.

In the case of mouse and human NF1 tumors, bioinformatics computer analysis suggested that deregulated Ras-GTPase signaling prompted MEK to stimulate the sustained activity of an enzyme called ERK. To confirm whether this molecular pathway is critical to NF1 tumor growth, researchers tested the MEK-blocking drug in genetically engineered mice.

The mice lacked expression of the NF1 gene and its tumor suppressing protein, causing the animals to develop benign neurofibromas. Scientists also transplanted human malignant peripheral nerve sheath tumor cells into a separate group of genetically receptive mice, which developed their own cancerous tumors.

Researchers then tested different doses of the drug to identify an optimal dose – one that would achieve the maximum amount of tumor shrinking efficiency with the least amount of toxicity. Treatment with PD0325901 reduced the abnormal growth of cells in both benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs). It also reduced the volume of tumor feeding blood vessels.

Treated mice with benign neurofibromas had significant shrinkage of their tumors after 60 days, compared to untreated mice. In mice implanted with human MPNSTs, the drug diminished cancerous tumor growth and doubled survival time to 52 days, as compared to untreated animals.

Researchers said overall shrinkage of MPNSTs was modest compared to that achieved in benign tumors, possibly because additional molecular pathways are involved in their formation. They said this suggests that MPNSTs may require a combinatory treatment that includes PD0325901 in conjunction with other therapies.

Mutations of the NF1 gene are frequently found in other cancers, such as glioblastoma, lung adenocarcinoma and ovarian cancer. The researchers said this could open the possibility of studying the Ras-MEK-ERK pathway as molecular target for treating these diseases.

Funding for the study came from: the DAMD Program on Neurofibromatosis for the NF1 Microarray Consortium (DODW81XWH-09-1-0135 and W81XWH-04-1-0273); the Children's Tumor Foundation for support to the NF1 Preclinical Consortium; a National Institutes of Health Bench to Bedside Award for MRI Analyses (NIH-P50-NS05753) and an American Recovery and Reinvestment Act supplement to NIH grant R01-NS28840. The drug was provided by the manufacturer, Pfizer Inc.

About Cincinnati Children's
Cincinnati Children's Hospital Medical Center ranks third in the nation among all Honor Roll hospitals in U.S. News and World Report's 2012 Best Children's Hospitals ranking. It is ranked #1 for neonatology and in the top 10 for all pediatric specialties. Cincinnati Children's is one of the top two recipients of pediatric research grants from the National Institutes of Health and a research affiliate of the University of Cincinnati College of Medicine. It is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education and innovation. Additional information can be found at www.cincinnatichildrens.org.

SOURCE Cincinnati Children's Hospital Medical Center

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
There are many considerations when moving applications from on-premise to cloud. It is critical to understand the benefits and also challenges of this migration. A successful migration will result in lower Total Cost of Ownership, yet offer the same or higher level of robustness. In his session at 15th Cloud Expo, Michael Meiner, an Engineering Director at Oracle, Corporation, analyzed a range of cloud offerings (IaaS, PaaS, SaaS) and discussed the benefits/challenges of migrating to each offe...
One of the hottest areas in cloud right now is DRaaS and related offerings. In his session at 16th Cloud Expo, Dale Levesque, Disaster Recovery Product Manager with Windstream's Cloud and Data Center Marketing team, will discuss the benefits of the cloud model, which far outweigh the traditional approach, and how enterprises need to ensure that their needs are properly being met.
In their session at 17th Cloud Expo, Hal Schwartz, CEO of Secure Infrastructure & Services (SIAS), and Chuck Paolillo, CTO of Secure Infrastructure & Services (SIAS), provide a study of cloud adoption trends and the power and flexibility of IBM Power and Pureflex cloud solutions. In his role as CEO of Secure Infrastructure & Services (SIAS), Hal Schwartz provides leadership and direction for the company.
In a recent research, analyst firm IDC found that the average cost of a critical application failure is $500,000 to $1 million per hour and the average total cost of unplanned application downtime is $1.25 billion to $2.5 billion per year for Fortune 1000 companies. In addition to the findings on the cost of the downtime, the research also highlighted best practices for development, testing, application support, infrastructure, and operations teams.
"We've just seen a huge influx of new partners coming into our ecosystem, and partners building unique offerings on top of our API set," explained Seth Bostock, Chief Executive Officer at IndependenceIT, in this SYS-CON.tv interview at 16th Cloud Expo, held June 9-11, 2015, at the Javits Center in New York City.
SYS-CON Events announced today that HPM Networks will exhibit at the 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. For 20 years, HPM Networks has been integrating technology solutions that solve complex business challenges. HPM Networks has designed solutions for both SMB and enterprise customers throughout the San Francisco Bay Area.
For IoT to grow as quickly as analyst firms’ project, a lot is going to fall on developers to quickly bring applications to market. But the lack of a standard development platform threatens to slow growth and make application development more time consuming and costly, much like we’ve seen in the mobile space. In his session at @ThingsExpo, Mike Weiner, Product Manager of the Omega DevCloud with KORE Telematics Inc., discussed the evolving requirements for developers as IoT matures and conducte...
The Software Defined Data Center (SDDC), which enables organizations to seamlessly run in a hybrid cloud model (public + private cloud), is here to stay. IDC estimates that the software-defined networking market will be valued at $3.7 billion by 2016. Security is a key component and benefit of the SDDC, and offers an opportunity to build security 'from the ground up' and weave it into the environment from day one. In his session at 16th Cloud Expo, Reuven Harrison, CTO and Co-Founder of Tufin,...
With SaaS use rampant across organizations, how can IT departments track company data and maintain security? More and more departments are commissioning their own solutions and bypassing IT. A cloud environment is amorphous and powerful, allowing you to set up solutions for all of your user needs: document sharing and collaboration, mobile access, e-mail, even industry-specific applications. In his session at 16th Cloud Expo, Shawn Mills, President and a founder of Green House Data, discussed h...
Mobile, social, Big Data, and cloud have fundamentally changed the way we live. “Anytime, anywhere” access to data and information is no longer a luxury; it’s a requirement, in both our personal and professional lives. For IT organizations, this means pressure has never been greater to deliver meaningful services to the business and customers.
Container technology is sending shock waves through the world of cloud computing. Heralded as the 'next big thing,' containers provide software owners a consistent way to package their software and dependencies while infrastructure operators benefit from a standard way to deploy and run them. Containers present new challenges for tracking usage due to their dynamic nature. They can also be deployed to bare metal, virtual machines and various cloud platforms. How do software owners track the usag...
The Internet of Everything (IoE) brings together people, process, data and things to make networked connections more relevant and valuable than ever before – transforming information into knowledge and knowledge into wisdom. IoE creates new capabilities, richer experiences, and unprecedented opportunities to improve business and government operations, decision making and mission support capabilities.
Puppet Labs has announced the next major update to its flagship product: Puppet Enterprise 2015.2. This release includes new features providing DevOps teams with clarity, simplicity and additional management capabilities, including an all-new user interface, an interactive graph for visualizing infrastructure code, a new unified agent and broader infrastructure support.
Chuck Piluso presented a study of cloud adoption trends and the power and flexibility of IBM Power and Pureflex cloud solutions. Prior to Secure Infrastructure and Services, Mr. Piluso founded North American Telecommunication Corporation, a facilities-based Competitive Local Exchange Carrier licensed by the Public Service Commission in 10 states, serving as the company's chairman and president from 1997 to 2000. Between 1990 and 1997, Mr. Piluso served as chairman & founder of International Te...
SYS-CON Events announced today that MobiDev, a software development company, will exhibit at the 17th International Cloud Expo®, which will take place November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. MobiDev is a software development company with representative offices in Atlanta (US), Sheffield (UK) and Würzburg (Germany); and development centers in Ukraine. Since 2009 it has grown from a small group of passionate engineers and business managers to a full-scale mobi...